Palladium-catalyzed carbon-monoxide-free aminocarbonylation of aryl halides using N-substituted formamides as an amide source

Article abstract of DOI:10.1021/jo200754v

A carbon-monoxide-free aminocarbonylation of various N-substituted formamides with aryl iodides and aryl bromides using palladium acetate and Xantphos is described. The developed methodology is applicable for a wide range of formamides and aryl halides containing different functional groups furnishing good to excellent yield of the corresponding products. N-substituted formamides are used as an amide source wherein a Vilsmeier-type intermediate plays a major role, thus eliminating the need of toxic carbon monoxide gas.

Full text of DOI:10.1021/jo200754v

NOTE
pubs.acs.org/joc
Palladium-Catalyzed Carbon-Monoxide-Free Aminocarbonylation of
Aryl Halides Using N-Substituted Formamides as an Amide Source
Dinesh N. Sawant, Yogesh S. Wagh, Kushal D. Bhatte, and Bhalchandra M. Bhanage*
Department of Chemistry, Institute of Chemical Technology, N. Parekh Marg, Matunga, Mumbai-400019, India
S Supporting Information
b
ABSTRACT: A carbon-monoxide-free aminocarbonylation of
various N-substituted formamides with aryl iodides and aryl
bromides using palladium acetate and Xantphos is described.
The developed methodology is applicable for a wide range of
formamides and aryl halides containing different functional
groups furnishing good to excellent yield of the corresponding
products. N-substituted formamides are used as an amide source
wherein a Vilsmeier-type intermediate plays a major role, thus eliminating the need of toxic carbon monoxide gas.
mides are very important functional groups in the synthesis
the use of microwave, in situ CO generation, and high reaction
temperature in the range of 180ꢀ190 °C restricts its applications.
Hiyama et al. were the first to use DMF as an amide source using
A
of numerous organic molecules, biologically active com-
1
pounds, and natural products. In 1974, Heck reported the first
palladium-catalyzed aminocarbonylation reaction, that is, reac-
tion between aryl, heterocyclic, and alkenyl halides with primary
or secondary amines and carbon monoxide (CO) for amide
Pd (dba) as catalyst and POCl a key additive in acidic
2 3 3
13
conditions. This involved a Vilsmeier-type intermediate play-
ing a vital role in the reaction, but protocol was specifically
limited to aryl iodides and DMF only. Lee et al. reported a
2
synthesis. After the first report, various protocols for aminocar-
bonylation were developed using CO as a source of the carbonyl
Ni(OAc) 4H O/phosphite catalytic system for aminocarbony-
2 2
3
3
group. However, CO is a highly lethal gas, with a main concern
lation using DMF as an amide source in basic conditions using
NaOMe or KOMe as base; further they extended the same
of its handling, storage, and transport. Also, the reaction setup
requires high-pressure reactors such as autoclaves, specialized gas
handling procedures, stainless steel tanks, and cylinders for safety
transportation, which restricts the utility of CO in the carbonyla-
tion reactions. Therefore, the development of newer CO-free
methods for the synthesis of amides isof significant interest among
14
protocol for other formamides. However, this protocol was not
applicable for aryl halides containing different functional groups.
Especially, most of the aryl iodides do not provide satisfactory
yield and undergo dehalogenation. Similarly, the yields for
amides other than N-methyl formamide and N-cyclohexylforma-
mide are quite low, and amides like diethylformamide, diisopro-
pyl formamide, formamide, etc. did not produce any product.
Recently, we reported a heterogeneous protocol using Pd/C
4
organic chemists. In recent years, many efforts have surged in this
direction, and various carbon monoxide alternatives for amide
5
6
synthesis, such as metal carbonyls like Mo(CO) , Ni(CO) , and
6
4
1
5
7
and phosphoryl chloride for CO-free aminocarbonylation.
W(CO) , were intensively investigated, while other sources like
carbamoylsilane, carbamoylstannanes, formamide, and DMF
6
8
9
10
11
However, the heterogeneous catalyst results in lowering the
yield of product and required 24 h for completion of the reaction,
and scope the is limited to aryl iodides and DMF only. Con-
sidering the limitations of the reported protocols, we herein
are attractive potential alternatives for toxic COgas. Incomparison
with organic material, inorganic metal carbonyl and their deriva-
tives are highly toxic and relatively much more expensive and most
of these protocols require specialized microwave equipment. The
use of carbamoylsilane and carbamoylstannane is limited to the
synthesis of N,N-dimethyl-substituted amide derivatives, and these
compounds are commercially not available. In addition to this,
carbamoylstannane is prepared via carbonylationꢀstannylation of
lithium amides, which is thermally unstable and toxic, hence
limiting its application.
report Pd(OAc) /Xantphos as a new catalytic system for CO-
2
free aminocarbonylation. Present protocol is applicable for all
types of formamide derivatives, aryl iodides, as well as aryl
bromides, providing good to excellent yield of desired products.
The developed methodology tolerated a wide range of functional
groups with an additional advantage of lower reaction time and
higher yields as compared to earlier protocols. While exploring a
cyanide-free protocol for cyanation reaction using formamide, we
observed that the same reaction conditions are applicable for
In literature, few reports exist on aminocarbonylation using
DMF as either a source of carbon monoxide or an amide.
12
16
Hallberg et al. employed DMF as a carbon monoxide source,
CO-free aminocarbonylation (Scheme 1).
where, in presence of a strong base and imidazole, DMF
decompose to CO, which reacts with amine and aryl halide,
providing corresponding aminocarbonylated product. However,
Received: April 11, 2011
Published: May 27, 2011
r 2011 American Chemical Society
5489
dx.doi.org/10.1021/jo200754v
|J. Org. Chem. 2011, 76, 5489–5494

The Journal of Organic Chemistry
NOTE
Scheme 1. CO-Free Aminocarbonylation of Aryl Halides
Using N-Substituted Formamides as an Amide Source
Table 3. Optimization of CO-Free Aminocarbonylation of
Aryl Halides Using N-Substituted Formamides
a
Pd/
L
mol
%
POCl
3
DMF
(mL)
time
(h)
yield
b
entry
(mmol)
(%)
effect of time
1
2
3
4
1:2
5
5
5
5
2
2
2
2
10
10
10
10
24
18
6
93
93
92
72
1:2
1:2
1:2
4
Table 1. Test Experiment for CO-Free Amniocarbonylation
of Iodobenzene (1a) with DMF (2a)
a
effect of catalyst loading
5
6
7
8
1:2
1:2
1:2
1:2
4
3
2
1
2
2
2
2
10
10
10
10
6
6
6
6
91
92
73
38
b
entry
Pd(OAc)
2
Xantphos
POCl
3
yield (%)
1
2
3
4
5
ꢀ
ꢀ
þ
þ
þ
ꢀ
þ
ꢀ
þ
þ
þ
þ
þ
ꢀ
þ
0
0
18
0
effect of metal to ligand ratio
9
0
1:1.5
1:1
3
3
2
2
10
10
6
6
82
70
93
1
a
Reaction conditions: 1a (1.0 mmol), 2a (10 mL/mmol), Pd(OAc)
5 mol %), Xantphos (10 mol %), POCl (2.0 mmol), 140 °C, 24 h
under nitrogen atmosphere. GC yield.
2
influence of POCl
3
concentration
(
3
b
11
1:2
1:2
3
3
2.5
1.5
10
10
6
6
93
78
12
a
influence of DMF concentration
Table 2. Screening of Metal Precursors and Ligands
1
1
1
1
1
3
4
5
6
7
1:2
1:2
1:2
1:2
1:2
3
3
3
3
3
2
2
2
3
2
8
6
5
3
1
6
6
6
6
6
92
91
92
84
45
a
2 3
Reaction conditions: 1a (1.0 mmol), 2a, Pd(OAC) , Xantphos, POCl ,
140 °C, under nitrogen atmosphere. GC yield.
b
b
entry
ligand
Pd catalyst
yield (%)
c
1
2
3
4
5
6
7
8
9
Xantphos
Pd(OAC)
Pd(OAC)
Pd(OAC)
Pd(OAC)
Pd(OAC)
Pd(OAC)
2
2
2
2
2
2
93
81
0
d
observed that bite angle might play a major role. Only Xantphos
and DPPF afforded 93 and 81% yield, respectively (Table 2,
entries 1 and 2), while other ligands such as DPPM DPPE,
DPPP, and DPPB exhibited no activity (Table 2, entries 3ꢀ6).
Therefore, with Xantphos as the choice of ligand, we studied the
effect of different metal precursors. It was observed that PdCl2
DPPF
e
DPPM
f
DPPE
0
g
DPPP
0
h
DPPB
0
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
PdCl
Pd(acac)
CuCl
Cu(OAC)
NiCl
Ni(OAC)
2
91
71
0
and Pd(OAc) provided similar yield of product (Table 2, entries
2
2
1 and 7). Hence, Pd(OAc) was selected for further study as it is
2
quite economical in comparison to PdCl , while other metal
2
2
precursors such as copper and nickel were unable to catalyze the
reaction (Table 2, entries 9ꢀ12).
1
1
1
0
1
2
2
0
2
0
Furthermore, we examined the influence of various reaction
parameters like time, catalyst loading, Lewis acids, effect of
solvents, and temperature (Table 3). To our surprise, during
the study, we observed completion of reaction within 6 h with
optimum yield of 92% (Table 3, entry 3). When the reaction was
2
0
a
Reaction conditions: 1a (1.0 mmol), 2a (10 mL/mmol), catalyst (5 mol %),
ligand (10 mol %), POCl (2.0 mmol), 140 °C, 24 h under nitrogen
atmosphere. GC yield. Xantphos = 4,5-bis(diphenylphosphino)-9,9-di-
methylxanthene. DPPF = 1,1-bis(diphenylphosphino)ferrocene. DPPM =
,1-bis(diphenylphosphino)methane. DPPE = 1,1-bis(diphenylphos-
3
b
c
d
e
f
1
carried out with 3 mol % of Pd(OAc) and 6 mol % of Xantphos,
2
g
h
phino)ethane. DPPP = 1,1-bis(diphenylphosphino)propane. DPPB =
,1-bis(diphenylphosphino)butane.
similar yields were obtained (Table 3, entry 6), while reducing
the catalyst loading further results in lower yields. The reduction
in the amount of Xantphos resulted in reduced yield of product
1
(
Table 3, entries 9 and 10), indicating that a 1:2 ratio of
Pd(OAc) to Xantphos is essential for higher yields (Table 3,
entry 6). In order to replace POCl , we screened various other
Lewis acids such as PCl , SOCl , FeCl , BF :OEt , etc. (refer to
Supporting Information, Table S1). Among the examined Lewis
acids, only PCl provided low yield of product, while use of other
Lewis acids was futile. It was observed that an increase of POCl3
Initially, the coupling of DMF with iodobenzene was chosen
as a model reaction and Pd(OAc) /Xantphos as a catalytic
2
2
system for optimization of reaction parameters. Test experiments
showed that Pd(OAc) , Xantphos, and POCl are essential to
3
2
3
3
2
3
3
2
obtain a higher yield of desired product (Table 1).
Observing the importance of ligand in reaction, we screened
various phosphine bidentate ligands (Table 2), and it was
3
5
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The Journal of Organic Chemistry
NOTE
a
Table 4. Influence of Temperature
concentration led to a slight increase in yield of product, while a
decrease in POCl concentration gave lower yield, addressing
b
3
entry
temperature (°C)
yield of 3a (%)
2
mmol of POCl as an optimized concentration (Table 3, entries
3
1
2
3
4
5
145
140
135
130
120
93
92
92
80
75
6, 11, and 12). Effect of DMF was also studied, which revealed
that 5 mL of DMF is essential for best results while lowering the
amount of DMF from 5 to 1 mL results in lower yield (Table 3,
entries 13ꢀ17). In order to reduce the amount of DMF further,
we screened various cosolvents, such as toluene, xylene, DMSO,
NMP, 1,4-dioxane, ethylene glycol, etc., along with DMF, but all
attempts were unsuccessful (see Supporting Information, Table
S2). The temperature study shows that 135 °C is the optimum
a
Reaction conditions: 1a (1.0 mmol), 2a (5 mL/mmol), Pd(OAc)
3 mol %), Xantphos (6 mol %), POCl (2.0 mmol), 6 h, under nitrogen
atmosphere. GC yield.
2
(
3
b
a
Table 5. Scope of CO-Free Aminocarbonylation of Aryl Iodides and Aryl Bromides
a
Reaction conditions: 1 (1.0 mmol), 2a (5 mL/mmol), Pd(OAc) (3 mol %), Xantphos (6 mol %), POCl (2.0 mmol), 135 °C, 6 h under nitrogen
2
3
b
c
atmosphere. Isolated yield. 1 (1.0 mmol), 2a (5 mL/mmol), Pd(OAc)
nitrogen atmosphere.
2
(5 mol %), Xantphos (10 mol %), POCl (2.0 mmol), 165 °C, 24 h under
3
5
491
dx.doi.org/10.1021/jo200754v |J. Org. Chem. 2011, 76, 5489–5494

The Journal of Organic Chemistry
NOTE
Table 6. Scope of N-Substituted Formamides for CO-Free
Amniocarbonylation
Table 7. Scope of N-Substituted Formamides for CO-Free
Amniocarbonylation
a
a
a
Bromobenzene (1.0 mmol), 2 (5 mL/mmol), Pd(OAc) (5 mol %),
2
a
Reaction conditions: iodobenzene (1.0 mmol), 2 (5 mL/mmol),
Xantphos (10 mol %), POCl (2.0 mmol), 165 °C, 24 h under nitrogen
3
b
Pd(OAc)
1
2
(3 mol %), Xantphos (6 mol %), POCl
3
(2.0 mmol),
atmosphere. Isolated yield.
b
35 °C, 6 h under nitrogen atmosphere. Isolated yield.
with decreased yields (Table 5, entry 9). By increasing catalyst
loading and improving reaction conditions, we achieved moderate
yields (Table 5, entry 10). The catalyst exhibited remarkable
activity where a variety of functional groups, such as OCH3,
temperature to obtain a higher yield of desired products
(
Table 4).
Thus, the optimized reaction conditions are 1a (1 mmol),
POCl (2 mmol), Pd(OAc) (3 mol %), and Xantphos (6 mol %),
NO , OH, and carbonyl, on the aryl bromide were well-tolerated,
3
2
2
in 5 mL/mmol of DMF at 135 °C, for a time period of 6 h.
In order to study the potential and general applicability of
developed methodology, various aryl iodides containing different
functional groups were investigated (Table 5). We observed that
electron-donatingaswell aselectron-withdrawinggroups provided
remarkable yield of products. A variety of functional groups
including methoxy, trifluoromethyl, nitro, hydroxyl, and carbonyl
were well-tolerated (Table 5, entries 1ꢀ6), whereas ortho substit-
uents furnished moderate yield (Table 5, entry 7) as this might be
due to steric hindrance. Similarly, 1-iodonaphthalene also exhib-
ited moderate yield of desired product (Table 5, entry 8). Next, we
attempted to widen the scope of our methodology for aryl
bromides and found that aryl bromides were well-tolerated but
furnishing good yield of expected products (Table 5, entries
11ꢀ14). Whereas ortho substitution on aryl bromides leads to a
decrease in yield (Table 5, entry 15), sterically hindered 1-iodo-
naphthalene provided a good yield of product (Table 5, entry 16).
The main goal behind exploring the protocol was to widen the
scope of various N-substituted formamides for CO-free amino-
carbonylation. In context, we screened a range of formamides
and observed that all kinds of formamides provided excellent
yield of products with iodobenzene (Table 6). The N,N-disub-
stituted sterically hindered formamides such as N,N-diethylfor-
mamide, N,N-dibutyl formamide, and N-methyl-N-phenylfor-
mamide reacted smoothly, furnishing excellent yields (Table 6,
entries 1ꢀ3). Second, we screened cyclic formamides such as
5
492
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The Journal of Organic Chemistry
-formylpiperidine and 4-formylmorpholine that provided the
highest yield of desired products (Table 6, entries 4 and 5). In the
case of N-monosubstituted formamide, it was observed that
N-hexylformamide and N-phenylformamide gave moderate
yield (Table 6, entries 6 and 7), while N-butylformamide and
N-benzylformamide offered an appreciable yield of desired
product (Table 6, entries 8 and 9).
To expand the scope of aryl bromides, coupling of various
formamides with bromobenzene was carried out. The N,N-
disubstituted sterically hindered formamides are well-tolerated,
giving moderate yield (Table 7, entries 1ꢀ3), while cyclic
formamides were found to react smoothly, providing the highest
yield of products (Table 7, entries 4 and 5). The N-monosub-
stituted formamides were also successfully applied to this system
NOTE
1
was added to the reaction mixture and was placed in and oil bath and
magnetically stirred at 165 °C for 24 h under complete nitrogen
atmosphere. After completion, the reaction mixture was cooled to room
temperature and was poured into a saturated solution of NaHCO
(50 mL). The product was extracted with ethyl acetate (4 ꢁ 20 mL).
The combined organic layers were dried over Na SO and evaporated to
3
2
4
afford the crude product which was purified by column chromatography
on silica gel (petroleum ether/ethyl acetate combination) to afford the
1
13
pure product. The product was confirmed by GCꢀMS and H and
C
NMR spectroscopic analysis.
1
3
þ
3a: GCꢀMS m/z (% relative intensity) 149 (M , 19), 148 (47),
1
1
3
3
05 (100), 77 (77), 51 (27); H NMR (300 MHz, CDCl
H), 3.11 (s, 3H), 7.40 (br s, 5H); C NMR (75 MHz, CDCl
9.7, 127.1, 128.4, 129.6, 136.4, 171.8.
3
) δ 2.97 (s,
) δ 35.4,
1
3
3
1
2
þ
3
b: GCꢀMS m/z (% relative intensity) 179 (M , 18), 178 (24),
(
Table 7, entries 6ꢀ9). It is noteworthy to mention that no
1
1
36 (9), 135 (100), 107 (16), 92 (13), 77 (23), 64 (9), 63 (5); H NMR
N-arylated product in any case of N-monosubstituted or unsub-
(
7
1
300 MHz, CDCl
3
) δ 3.0 (br s, 6H), 3.83 (s, 3H), 6.69ꢀ6.92 (m, 2H),
stituted formamide was obtained.
1
3
.39ꢀ7.42 (m, 2H); C NMR (75 MHz, CDCl ) δ 35.3, 39.6, 55.1,
3
In summary, we developed a new protocol for CO-free
aminocarbonylation wherein all types of N-substituted forma-
mides can be coupled with aryl iodides as well as aryl bromides,
providing an excellent yield of desired products. Lower reaction
time adds an additional credit to the present study. In general, all
kinds of functional groups were very well-tolerated, offering
higher yields. Furthermore, neither the reaction required external
toxic CO gas nor there was formation of in situ CO as it involved
a Vilsmeier-type intermediate utilizing formamides used as amide
source instead of a toxic CO source. This advancement in CO-
free aminocarbonylation reaction thus is appealing because the
developed protocol will prove to be an attractive alternative to
the reported methods for aminocarbonylation reactions.
13.3, 128.1, 128.8, 160.3, 171.3.
1
5
þ
3
c: GCꢀMS m/z (% relative intensity) 194 (M , 39), 193 (100),
1
(
77 (12), 150 (86), 147 (19), 120 (33), 104 (66), 92 (35), 76 (50), 50
1
20), 44 (11); H NMR (300 MHz, CDCl ) δ 2.97 (s, 3H), 3.14 (s, 3H),
.58ꢀ7.62 (m, 2H), 8.26ꢀ8.29 (m, 2H); C NMR (75 MHz, CDCl
3
13
7
3
)
δ 35.3, 39.2, 123.7, 128.0, 142.4, 148.2, 169.2.
12
þ
3
d: GCꢀMS m/z (% relative intensity) 163 (M , 29), 162 (28),
1
1
1
1
1
48 (9), 119 (100), 118 (10), 91 (72), 65 (26).
17
þ
þ
3
e: GCꢀMS m/z (% relative intensity) 165 (M , 19), 164 (33),
21 (100), 93 (27), 65 (27), 44 (28).
18
3
f: GCꢀMS m/z (% relative intensity) 191 (M , 37), 190 (45),
48 (11), 147 (100), 119 (25), 104 (9), 91 (24), 76 (15), 43 (20).
1
2
þ
3
g: GCꢀMS m/z (% relative intensity): 179 (M , 18), 178 (24),
36 (9), 135 (100), 107 (16), 92 (13), 77 (23), 64 (9), 63 (5).
1
2
þ
3
h: GCꢀMS m/z (% relative intensity) 199 (M , 41), 198 (18),
’
EXPERIMENTAL SECTION
56 (13), 155 (100), 128 (11), 127 (83), 126 (15), 77 (11).
1
19
þ
General: All products are well-known compounds. H NMR and
C NMR spectra were recorded on a 300 MHz spectrometer in CDCl3.
4a: GCꢀMS m/z (% relative intensity) 177 (M , 14), 176 (36),
1
1
3
105 (100), 77 (43), 51 (10); H NMR (300 MHz, CDCl
3
) δ 1.19ꢀ1.31
Chemical shifts are reported in parts per million (δ) relative to
tetramethylsilane as internal standard. J (coupling constant) values were
reported in hertz. Splitting patterns of proton are described as s (singlet),
d (doublet), t (triplet), and m (multiplet). GC analysis was carried out
on a gas chromatograph equipped with a flame ionization detector using
a fused capillary column. All products obtained and discussed in this
work have been previously reported and characterized by suitable
technique.
(br d, 6H), 3.33 (br s, 2H), 3.62 (br s, 2H), 7.44ꢀ7.46 (m, 5H); IR
(neat) 2973, 2935, 2875, 1631, 1456, 1382, 1287, 1220, 1097, 1027, 942,
ꢀ
1
872, 786, 705, 628 cm
.
2
0
5a: GCꢀMS m/z (% relative intensity) 233 (8), 232 (7), 190 (13),
1
105 (100), 77 (28); H NMR (300 MHz, CDCl ) δ 0.71 (br s, 3H),
3
0.92ꢀ1.07 (br d, 5H), 1.40 (br s, 4H), 1.60 (br s, 2H), 3.14 (br s, 2H),
3.44 (br s, 2H), 7.28ꢀ7.29 (m, 5H); IR (neat) 2932, 2958, 2872, 1635,
1578, 1495, 1465, 1423, 1377, 1297, 1265, 1192, 1102, 956, 922, 786,
ꢀ
1
General Experimental Procedure for Aminocarbonylation
of DMF with Aryl Iodides: A mixture of iodobenzene (1 mmol),
731, 700, 651 cm .
2
1
6a: GCꢀMS m/z (% relative intensity) 211 (26), 118 (5), 105
1
Pd(OAc)
2
(3 mol %), and Xantphos (6 mol %) in DMF (5 mL/mmol)
3
(100), 77 (59), 51 (13); H NMR (300 MHz, CDCl ) δ 3.68 (s, 3H),
was placed in a 25 mL two-necked round-bottom flask equipped with a
condenser at room temperature under nitrogen atmosphere. Then POCl3
7.21ꢀ7.48 (m, 10H); IR (neat) 3060, 2936, 1640, 1595, 1494, 1446,
1419, 1366, 1302, 1176, 1106, 1076, 1026, 922, 791, 769, 724, 701, 654,
ꢀ
1
(2 mmol) was added to the reaction mixture and was placed in an oil bath
579 cm .
7
and magnetically stirred at 135 °C for 6 h under complete nitrogen
atmosphere. After completion, the reaction mixture was cooled to room
7a: GCꢀMS m/z (% relative intensity) 190 (3), 189 (30), 188
1
(100), 106 (9), 105 (99), 77 (60), 51 (13); H NMR (300 MHz,
temperature and was poured into a saturated solution of NaHCO
50 mL). The product was extracted with ethyl acetate (4 ꢁ 20 mL).
The combined organic layers were dried over Na SO and evaporated to
3
CDCl
3
) δ 1.73ꢀ1.80 (br d, 6H), 3.52 (br s, 2H), 3.80 (br s, 2H), 7.51 (s,
(
5H); IR (neat) 3026, 3057, 2998, 2936, 2855, 1630, 1577, 1465, 1431,
ꢀ1
1369, 1275, 1110, 1003, 853, 787, 731, 707, 632 cm .
2
4
5
c
afford the crude product which was purified by column chromatography
on silica gel (petroleum ether/ethyl acetate combination) to afford the
8a: GCꢀMS m/z (% relative intensity) 191 (12), 190 (32), 176 (8),
1
105 (100), 86 (15), 77 (53), 56 (15), 51 (14); H NMR (300 MHz,
1
13
pure product. The product was confirmed by GCꢀMS and H and
C
CDCl
) δ 3.62ꢀ3.81 (br s, 8H), 7.53 (br s, 5H); IR (neat) 2979, 2901,
3
NMR spectroscopic analysis.
General Experimental Procedure for Aminocarbonylation
2859, 1626, 1426, 1361, 1300, 1271, 1111, 1073, 1020, 933, 840, 796,
ꢀ1
736, 712, 592 cm .
7
þ
of DMF with Aryl Bromides. A mixture of bromobenzene (1 mmol),
9a: GCꢀMS m/z (% relative intensity) 203 (M , 27), 122 (76), 105
1
Pd(OAc)
2
(5 mol %), and Xantphos (10 mol %) in DMF (5 mL/mmol)
(100), 79 (13), 77 (54); H NMR (300 MHz, CDCl
) δ 1.43ꢀ1.60 (m,
3
was placed in a 25 mL two-necked round-bottom flask equipped with a
5H), 1.79ꢀ1.95 (m, 3H), 2.15ꢀ2.20 (m, 2H), 4.11ꢀ4.15 (br s, 1H),
6.43 (br s, 1H), 7.45ꢀ7.66 (m, 3 H), 7.91ꢀ7.99 (m, 2H); IR (neat)
condenser at room temperature under nitrogen. Then POCl (2 mmol)
3
5
493
dx.doi.org/10.1021/jo200754v |J. Org. Chem. 2011, 76, 5489–5494

The Journal of Organic Chemistry
NOTE
3
6
329, 3238, 3069, 2929, 2851, 1627, 1534, 1488, 1329, 1151, 1083, 890,
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ꢀ1
94 cm
.
7
þ
10a: GCꢀMS m/z (% relative intensity) 197 (M , 32), 106 (7), 105
1
(100), 77 (56), 51 (13); H NMR (300 MHz, CDCl
3
) δ 7.12ꢀ7.18 (m,
1
7
1
5
H), 7.33ꢀ7.39 (m, 2H), 7.43ꢀ7.56 (m, 3 H), 7.64ꢀ7.68 (m, 2H),
.84ꢀ7.89 (m, 2H), 8.18 (br s, 1H); IR (neat) 3344, 3054, 1655, 1599,
531, 1439, 1322, 1261, 1075, 1028, 927, 910, 885, 790, 749, 716, 690,
83, 508 cm
ꢀ1
.
7
þ
1
1a: GCꢀMS m/z (% relative intensity) 211 (M , 11), 210 (70),
1
2
09 (26), 106 (27), 105 (100), 91 (10), 77 (63), 51 (15); H NMR (300
) δ 4.60 (m, 2H), 6.85 (br s, 1H), 7.32ꢀ7.51 (m, 8H),
.78ꢀ7.81 (m, 2H); IR (neat) 3327, 3059, 1640, 1542, 1418, 1314,
MHz, CDCl
3
7
1
ꢀ1
259, 1185, 1057, 990, 727, 693, 667 cm
.
(
6) Corey, E. J.; Hegedus, L. S. J. Am. Chem. Soc. 1969,
1, 1233–1234.
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7
þ
1
2a: GCꢀMS m/z (% relative intensity) 177 (M , 9), 176 (2), 135
9
1
(
24), 134 (17), 105 (100), 77 (41), 51 (12); H NMR (300 MHz, CDCl
δ 0.94 (t, 3H), 1.32ꢀ1.42 (m, 2H), 1.51ꢀ1.61 (m, 2H), 3.37ꢀ3.43
m, 2H), 6.80 (br s, 1H), 7.33ꢀ7.47 (m, 3H), 7.76ꢀ7.79 (m, 2H).
3
)
(
(
(b) Cunico, R. F.; Maity, B. C. Org. Lett. 2003, 5, 4947–4949. (c) Cunico,
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(
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988, 569–573.
10) Wan, Y.; Alterman, M.; Larhed, M.; Hallberg, A. J. Comb. Chem.
003, 5, 82–84.
’
ASSOCIATED CONTENT
1
2
1
13
(
S
Supporting Information. Copies of H and C NMR of
b
the products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(
(
11) Muzart, J. Tetrahedron 2009, 65, 8313–8323.
12) DMF as CO source: Wan, Y.; Alterman, M.; Larhed, M.;
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13) DMF as amide source in acidic condition: Hosoi, K.; Nozaki,
K.; Hiyama, T. Org. Lett. 2002, 4, 2849–2851.
14) DMF as amide source in basic condition: (a) Ju, J.; Jeong, M.;
Moon, J.; Jung, H. M.; Lee, S. Org. Lett. 2007, 9, 4615–4618. (b) Jo, Y.;
Ju, J.; Choe, J.; Song, K. H.; Lee, S. J. Org. Chem. 2009, 74, 6358–6361.
’
AUTHOR INFORMATION
(
Corresponding Author
(
*
Phone: þ 91-22 3361 1111/2222. Fax: þ91-22 2414 5614.
E-mail: bm.bhanage@ictmumbai.edu.in, bhalchandra_bhanage@
yahoo.com.
(
15) Tambade, P. J.; Patil, Y. P.; Bhanushali, M. J.; Bhanage, B. M.
Tetrahedron Lett. 2008, 49, 2221–2224.
16) Sawant, D. N.; Wagh, Y. W.; Tambade, P. J.; Bhatte, K. D.;
Bhanage, B. M. Adv. Synth. Catal. 2011, 353, 781–787.
17) Eckardt, R.; Carstens, E.; Fiedler, W. Pharmazie 1975, 30,
33–637.
(
’
ACKNOWLEDGMENT
(
The authors are grateful to the University Grant Commission,
6
2
2
India, for financial support under UGC SAP program, Green
Technology Centre of Institute of Chemical Technology, India.
(
18) Karimi, F.; Langstr €o m, B. Eur. J. Org. Chem. 2003, 11,
132–2137.
(19) Hans, J. J.; Driver, R. W.; Burke, S. D. J. Org. Chem. 2000, 65,
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